Process for preparing chiral compounds from recemic epoxides by using chiral salen catalysts

ABSTRACT

The present invention relates to chiral salen catalysts and a process for preparing chiral compounds from racemic epoxides by using them. More particularly, the present invention is to provide chiral salen catalysts and its use for producing chiral compounds such as chiral epoxides and chiral 1,2-diols economically in high yield and high optical purity by performing stereoselective hydrolysis of racemic epoxides, wherein the chiral salen catalyst comprises a cationic cobalt as a center metal of chiral salen ligand and counterions having weak nucleophilic property to resolve disadvantages associated with conventional chiral salen catalysts, and can be used continuously without any activating process of used catalysts because it does not loose a catalytic activity during the reaction process.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to chiral salen catalysts and a processfor preparing chiral compounds from racemic epoxides by using them. Moreparticularly, the present invention is to provide chiral salen catalystsand its use for producing chiral compounds such as chiral epoxides andchiral 1,2-diols economically in high yield and high optical purity byperforming stereoselective hydrolysis of racemic epoxides, wherein thechiral salen catalyst comprises a cationic cobalt as a center metal ofchiral salen ligand and counterions having weak nucleophilic property toresolve disadvantages associated with conventional chiral salencatalysts, and can be used continuously without any activating processof used catalysts because it does not loose a catalytic activity duringthe reaction process.

Chiral epoxides or chiral 1,2-diols have been widely used to preparepharmaceuticals and agriculture products having optical properties (U.S.Pat. No. 5,071,868; Tetrahedron Lett., Vol. 28, No. 16, 1783, 1987; J.Org. Chem., Vol. 64, 8741, 1999). Even if these chiral epoxides orchiral 1,2-diols having high optical purity are very usefulindustrially, use of these compounds has been restricted because thepreparation of such compounds is too difficult to produce in a largescale with low manufacturing price.

A preparation method of chiral epichlohydrins as one of chiral expoxidesis disclosed using microorganism in EP 431,970 and JP 90-257895 and94-211822. However, it is not recommended because the productivity islow and it requires two-step process. Another preparation method ofchiral epichlohydrins from chiral sulfonyloxyhaloalcohol derivativesobtained from mannitol derivatives is disclosed in U.S. Pat. No.4,408,063; and J. Org. chem., Vol 43, 4876, 1978. Another preparationmethod of chiral epichlohydrins from 3-chloro-1,2-propanediol is alsodisclosed in Syn. Lett No. 12, 1927, 1999. However, these processes arerequired multi-step syntheses, so that they are also deficient to usefor the industrial purpose.

Methods for preparing chiral expoxides generally use a chiral catalysthaving stereoselectivity which hydrolyzes stereoselectively only oneisomer from racemic epoxides mixed 50 and 50 of each isomer and leavesthe un-hydrolyzed isomer in the reaction medium. However, the chiralcatalyst used for said stereoselective hydrolysis is usually expensive.Therefore, if it cannot be re-used, it becomes difficult to use for theindustrial purpose.

Stereoselective hydrolyses of chiral epoxides using chiral salencatalyst as a chiral catalyst are recently disclosed in Science, Vol.277, 936, 1997; U.S. Pat. Nos. 5,665,890 and 5,929,232; and WO00/09463and WO91/14694. It has been reported that the use of chiral salencatalyst provides higher yield with higher optical purity compared touses of other chiral catalysts. However, it is reported that afterhydrolysis of a racemic epoxide using conventional chiral salencatalyst, the product chiral epoxide is racemized as time goes in pages86-87 of WO00/09463. When this hydrolysis is performed for massproduction, the racemization of the product becomes deepened since ittakes longer to perform the distillation to obtain the desired product,thus resulting in decrease of optical purity of the chiral epoxide.Therefore, the use of chiral salen catalyst in the production of chiralepoxides is limited for the above-mentioned reasons.

Further, when conventional chiral salen catalysts are reused, itrequires an activation process after each use because activities thereofare rapidly decreased. Even if the catalyst is activated after used, theoptical activity of the product prepared by using reused catalyst isremarkably lower than that of the product prepared by using freshcatalyst. Thus, there is limited to reuse. Such problems increase themanufacturing price of producing chiral epoxides.

Consequently, demand to produce chiral compounds such as chiral epoxidesor chiral 1,2-diols efficiently and economically has been highlyincreased with the importance of such compounds to preparepharmaceuticals and agriculture products.

SUMMARY OF THE INVENTION

The present invention has been completed by developing novel chiralsalen catalyst comprising a cobalt as a center metal and its counterionsof PF₆- or BF₄- to prevent from loosing activities of chiral catalystsand racemization of chiral products because conventional chiral salencatalysts having acetate groups loose their activities or functionalgroups such as acetate groups thereof.

In other words, it is important to select appropriate counterions bondedto the center metal in chiral salen catalysts used in stereoselectivehydrolyses of racemic epoxides. For example, chiral catalysts havingnucleophilic groups such as acetate and halogen group as counterionsdeteriorate optical purity of products and counterions bonded weakly tothe center metal in chiral catalysts can be dissociated during thereaction process, resulting in diminished catalytic activity.

The chiral salen catalyst of the present invention not only keeps itsactivity but also provides excellent production of chiral epoxideswithout racemization by comprising a cobalt center metal and counterionsof PF₆- or BF₄-. Therefore, an object of the present invention is toprovide chiral salen catalysts which keep excellent catalytic activityafter used, thus simplifing the manufacturing process since it does notrequire activation process of the used catalyst and do not contributefor racemization of produced products.

Another object of the present invention is to provide an economicalprocess for preparing chiral epoxides and chiral 1,2-diols from racemicepoxides by using said chiral salen catalyst in high yield and highoptical purity.

BRIEF DESCRIPTION OF THE PRESENT INVENTION

FIG. 1 represents a graph comparing an optical purity of productsproduced by using conventional chiral salen catalyst having acetategroup with that using the chiral salen catalyst of the present inventionover reaction time.

FIG. 2 represents a graph comparing an optical purity of productsproduced by using conventional chiral salen catalyst having acetategroup with that using the chiral salen catalyst of the present inventionover number of times it is used.

FIG. 3 represents a grape comparing degrees of racemization of productsproduced by using conventional chiral salen catalyst having acetategroup and conventional chiral salen catalyst having bromide group withthat using the chiral salen catalyst of the present invention overreaction time.

FIG. 4 represents UV data of the catalyst before and after reactionusing the chiral salen catalyst of the present invention.

FIG. 5 represents UV data of the catalyst before and after reactionusing the chiral salen catalyst having acetate group.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is characterized by using chiral salen catalystsexpressed by the following formula (1) in preparation of chiral epoxidesor chiral 1,2-diols from racemic epoxides,

wherein X₁, X₂, X₃, X₄, X₅, X₆, X₇, and X₈ represent individually ahydrogen atom or C₄-C₁₀ alkyl; Y₁ and Y₂ represent individually ahydrogen atom or C₁-C₅ alkyl; Z represents PF₆, or BF₄; R₁ and R₂represent individually a hydrogen atom, C₄-C₁₀ alkyl, or unsubstitutedor C₁-C₄ alkyl substituted phenyl, wherein one of R₁ and R₂ should be ahydrogen atom, or R₁ and R₂ are bonded each other to be —(CH₂)_(n)—(where, n is an integer of 3 to 6) or —(CH₂)_(m)—Q—(CH₂)_(m)— (where, mis an integer of 1 to 2, an oxygen atom or NH).

In the stereoselective hydrolysis of racemic epoxides to chiral epoxidesor chiral 1,2-diols, the present invention performs in the presence ofsaid chiral salen catalyst of formula (1).

The present invention is described in detail as set forth hereunder.

The present invention relates to the process for preparing opticallypure epoxides or 1,2-diols from racemic epoxides by stereoselectivehydrolysis in the presence of the chiral salen catalyst which can bereused continuously without an activation process after used and doesnot affect racemization of the produced products.

The chiral salen catalyst of formula (1) can be easily prepared by aknown method disclosed in Tetrahedron Asymmetry, Vol. 2, No. 7, 481,1991; and J. Org. Chem., Vol. 59, 1939, 1994. As shown in Scheme 1, itis prepared by treatment of the salen compound of formula (2) withcobalt(II) acetate and ferrocenium derivative in an organic solvent,

wherein X₁, X₂, X₃, X₄, X₅, X₆, X₇, X₈, Y₁, Y₂, Z, R₁, and R₂ are sameas previously defined.

The chiral salen catalyst of formula (1) can be used by immobilizing onthe stationary phase such as zeolite.

The mechanism of preparing chiral epoxides or chiral 1,2-diols fromracemic epoxides in the presence of the chiral salen catalyst of formula(1) by stereoselective hydrolysis is shown in Scheme 2,

wherein R represents unsubstituted or halogen-substituted C₁-C₁₀ alkyl,unsubstituted or halogen-substituted C₃-C₈ cycloalkyl, or unsubstitutedor halogen-substituted phenyl; I-RR represents represents a chiral salencatalyst of formula (1), wherein R₁ is a hydrogen atom; I-SS representsa chiral salen catalyst of formula (1), wherein R₂ is a hydrogen atom.

The stereoselective hydrolysis of Scheme 2 is described in more detailhereinafter.

Racemic epoxide compound of formula (3), 0.4-0.8 equivalents of waterand over 0.001 mol % of a chiral salen catalyst, preferably 0.1-5 mol %,are reacted at a temperature of −10 to 30° C., preferably 5 to 25° C.After the reaction is completed, a chiral epoxide, which is (R)-4 or(S)-4, is obtained by fractional distillation. The chiral salen catalystis recovered and a chiral 1,2-diol, which is (R)-5 or (S)-5, is obtainedfrom the residue by using organic solvent. The recovered catalyst isre-used for hydrolysis of fresh racemic epoxide to produce chiralepoxide or chiral 1,2-diol without any activation process.

When the chiral salen catalyst of formula (1), where R₁ is a hydrogenatom, (hereafter referring to as “I-RR”) is used for the stereoselectivehydrolysis, (R)-epoxide or (S)-1,2-diol is produced, while when thechiral salen catalyst of formula (1), where R₂ is a hydrogen atom,(hereafter referring to as “I-SS”) is used, (S)-epoxide or (R)-1,2-diolis produced.

FIGS. 1 and 2 are graphs comparing a reaction rate and optical purity ofconventional chiral salen catalyst having acetate group (comparativecatalyst 1) with those of chiral salen catalyst (I-SS-1) of the presentinvention over reaction time.

The use of the chiral salen catalyst of the present invention showsfaster reaction rate and higher optical purity (over 99% ee) than thatof the conventional chiral salen catalyst having acetate group. It isfurther proved that the chiral salen catalyst of the present inventioncan be used continuously without any activation process, while theconventional chiral salen catalyst having acetate group has to beactivated with acetic acid after each use because it looses itscatalytic activity and the reaction using recovered catalyst takes muchlonger to obtain over 99% ee of optical purity of the product than thatusing fresh catalyst.

FIG. 3 represents a graph comparing degrees of racemization of productsproduced by using conventional chiral salen catalyst having acetategroup (OAc; (comparative catalyst 2) and conventional chiral salencatalyst having bromide group (Br; (comparative catalyst 3) with thatusing the chiral salen catalyst (I-RR-1) of the present invention overreaction time.

In FIG. 3, when the chiral salen catalyst of the present invention isused, there is no or little of racemization over reaction of time, whilewhen conventional chiral salen catalyst having acetate group (OAc;(comparative catalyst 2) or conventional chiral salen catalyst havingbromide group (Br; (comparative catalyst 3) is used, the degree ofracemization becomes higher over reaction time, resulting in loweringoptical purity of the corresponding product because the conventionalchiral salen catalysts contain counterions having a nuclophilic group.In the mass production of chiral epoxides, it will take longer reactiontime to distill the desired product. Therefore, it is expected that useof the chiral salen catalyst of the present invention contributes toproduce optically pure chiral epoxide, while use of the comparativecatalyst 2 or 3 produces in lowered optical purity due to racemizationduring distillation process.

Hereunder is given the more detailed description of the presentinvention using examples. However, it should not be construed aslimiting the scope of the present invention.

EXAMPLE 1

Preparation of(S,S)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamincobalt(III) hexafluorophosphate

1 Equivalent of(S,S)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine and1,2 equivalent of cobalt(II)acetate.4H₂O were added to ethanol andrefluxed for 5 hrs while stirring. The reaction mixture was filtered andwashed with small amount of ethanol. The obtained solid, 1 equivalent offerrocenium hexafluorophosphate and acetonitrile were mixed and refluxedfor 1 hr while stirring, and acetonitrile was then evaporated undervacuum. Hexane was added to the residue and stirred for 30 min andfiltered to obtain the target product. IR 1060, 1110, 1170, 1195, 1210,1295, 1410, 1480, 1500, 1510, 1605, 1645 cm⁻¹; ³¹P NMR(CDCl₃) δ(H₃PO₄,ppm)−144.49[m, J(³¹P, ¹⁹F)=1.77 KHz]

EXAMPLE 2

Preparation of(R,R)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediaminocobalt(III) hexafluorophosphate

The reaction was performed in the same manner as Example 1 except that(R,R)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine wasused instead of(S,S)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine toobtain the target product. IR 1060, 1110, 1170, 1195, 1210, 1295, 1410,1480, 1500, 1510, 1605, 1645 cm⁻¹; ³¹P NMR(CDCl₃) δ(H₃PO₄,ppm)−144.49[m, J(³¹P, ¹⁹F)=1.77 KHz]

EXAMPLE 3

Preparation of(S,S)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediaminocobalt(III) tetrafluoroborate

1 Equivalent of(S,S)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine and1.2 equivalents of cobalt(II)acetate.4H₂O were added to ethanol andrefluxed for 5 hrs while stirring. The reaction mixture was filtered andwashed with small amount of ethanol at room temperature. The obtainedsolid, ferrocenium tetrafluoroborate and acetonitrile were mixed andrefluxed for 1 while stirring. Acetonitrile was then evaporated undervacuum. Hexane was added to the residue and stirred for 30 min, followedby filtration to obtain the target product.

EXAMPLE 4 Preparation of (R,R)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamino cobalt(III)tetrafluoroborate

The reaction was performed in the same manner as Example 3 except that(R,R)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine wasused instead of(S,S)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine toobtain the target product.

EXAMPLE 5

Preparation of(S)-N-(3,5-di-t-butylsalicylidene)-(S)-N′-(salicylidene)-1,2-cyclohexanediaminocobalt(III) hexafluorophosphate

The reaction was performed in the same manner as Example 1 except that(S)-N-(3,5-di-t-butylsalicylidene)-(S)-N′-(salicylidene)-1,2-cyclohexanediaminewas used instead of(S,S)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine toobtain the target product.

IR 840, 890, 990, 1020, 1110, 1185, 1220, 1255, 1270, 1285, 1370, 1400,1450, 1480, 1560, 1610, 1640 cm⁻¹

EXAMPLE 6

(R)-N-(3,5-di-t-butylsalicylidene)-(R)-N′-(salicylidene)-1,2-cyclohexanediaminocobalt(III) hexafluorophosphate

The reaction was performed in the same manner as Example 1 except that(R)-N-(3,5-di-t-butylsalicylidene)-(R)-N′-(salicylidene)-1,2-cyclohexanediaminewas used instead of(S,S)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine toobtain the target product.

EXAMPLE 7

Preparation of(S)-N-(3,5-di-t-butylsalicylidene)-(S)-N′-(salicylidene)-1,2-cyclohexanediaminocobalt(III) tetrafluoroborate

The reaction was performed in the same manner as Example 3 except that(S)-N-(3,5-di-t-butylsalicylidene)-(S)-N′-(salicylidene)-1,2-cyclohexanediaminewas used instead of(S,S)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine toobtain the target product.

EXAMPLE 8

Preparation of(R)-N-(3,5-di-t-butylsalicylidene)-(R)-N′-(salicylidene)-1,2-cyclohexanediaminocobalt(III) tetrafluoroborte

The reaction was performed in the same manner as Example 3 except that(R)-N-(3,5-di-t-butylsalicylidene)-(R)-N′-(salicylidene)-1,2-cyclohexanediaminewas used instead of(S,S)-NN′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine toobtain the target product.

EXAMPLE 9

Preparation of(R,R)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediaminocobalt(III) bromide

1 equivalent of(R,R)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine and1.2 equivalents of cobalt(II)acetate.4H₂O were added to ethanol andrefluxed for 5 hrs while stirring. The reaction mixture was filtered andwashed with small amount of ethanol at room temperature. The obtainedsolid, 0.5 equivalents of bromine, and dichloromethane were added andrefluxed for 1 hr while stirring and dichloromethane was evaporatedunder vacuum to obtain the target product.

EXAMPLE 10

Preparation of(R,R)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamino cobalt(III) chloride

1 equivalent of(R,R)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine and1.2 equivalents of cobalt(II)acetate.4H₂O were added to ethanol andrefluxed for 5 hrs while stirring. The reaction mixture was filtered andwashed with small amount of ethanol at room temperature. The obtainedsolid, 0.5 equivalents of chlorine gas, and dichloromethane were addedand refluxed for 1 hr while stirring and dichloromethane was evaporatedunder vacuum to obtain the target product.

EXAMPLE 11

Preparation of(R,R)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediaminocobalt(III) iodide

1 equivalent of(R,R)-N,N′-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamine and1.2 equivalents of cobalt(II)acetate.4H₂O were added to ethanol andrefluxed for 5 hrs while stirring. The reaction mixture was filtered andwashed with small amount of ethanol at room temperature. The obtainedsolid, 0.5 equivalents of iodine, and dichloromethane were added andrefluxed for 1 hr while stirring and dichloromethane was evaporatedunder vacuum to obtain the target product.

EXPERIMENTAL EXAMPLE 1

Preparation of (R)-epichlorohydrin or (S)-epichlorohydrin

Each 100 g of racemic epichlorohydrin was added to 0.25 mol % of thecatalyst prepared in Examples 1 to 8 and cooled to 5° C. Each 13.6 g ofwater was added slowly to each reaction mixture and then stirred at 20°C. for 4 hrs. Each reaction mixture was performed for fractionaldistillation under vacuum to obtain (R)[or (S)]-epichlorohydrin.Dichloromethane and water were added to the residue and the usedcatalyst was obtained from dichloromethane layer which was furtherevaporated under vacuum. The recovered catalyst without any activationprocess was reused for another hydrolysis reaction of racemicepichlorohydrin continuously to obtain (R)[or (S)]-epichlorohydrin withover 99% ee of optical purity.

As shown in FIG. 4 representing UV data of I-SS-1 prepared in Example 1before and after the hydrolysis reaction, the data before the reactionwas not changed from that after.

COMPARATIVE EXPERIMENTAL EXAMPLE 1

Preparation of (R)-epichlorohydrin

(R)-epichlorohydrin was prepared in the same manner as ExperimentalExample 1 by using the conventional chiral salen catalyst having acetategroup (comparative catalyst 1). When the used catalyst was used for nextreaction without any activation process, (R)-epichlorohydrin with 17% eeof optical purity was prepared. After the second reaction, the usedcatalyst was activated by a known method (Science, Vol. 277, 936, 1997).The used catalyst was added in toluene and 2 equivalent of acetic acidand stirred for 1 hr under atmosphere condition and the solvent was thenevaporated under vacuum to obtain recovered catalyst. When the thirdreaction was performed by using the recovered catalyst, the reactiontook 7 to 8 hrs under the same reaction condition to obtain(R)-epichlorohydrin with lower than 99% ee of optical purity, while ittook only 4 hr when the fresh catalyst was used. The result wassummarized in Table 1.

TABLE 1 Optical Reaction Catalyst Nos. of time purity (% ee) Ave. yieldtime Comparative 1^(st) >99.8 80% 4 hr catalyst 1 2^(nd) (w/o 17 — 8 hrhaving activation) acetate group 3^(rd) <99 80% 8 hr (w/activation)I-SS-1 1^(st) >99.8   80.4% 4 hr (or I-RR-1) 4^(th) >99.8 6 hr8^(th) >99.8 8 hr 10^(th ) >99.4 12 hr  I-SS-2 1^(st) >99.8 80% 4 hr (orI-RR-2) 5^(th) >99.8 6 hr 6^(th) >99.7 10 hr  7^(th) >99.4 12 hr  I-SS-31^(st) >99.8 80% 4 hr (or I-RR-3) 4^(th) >99.8 6 hr 8^(th) >99.6 8 hr10^(th ) >99.3 12 hr  I-SS-4 1^(st) >99.8 78% 4 hr (or I-RR-4)4^(th) >99.8 6 hr 5^(th) >99.5 8 hr 6^(th) >99.1 12 hr 

In FIG. 5 representing UV data of the catalyst before and after reactionusing the chiral salen catalyst (comparative catalyst 1) having acetategroup, it indicated that acetate group of the comparative catalyst 1 wasdissociated after the reaction.

COMPARATIVE EXPERIMENTAL EXAMPLE 2

Comparative of Changes in Optical Purity of (S)-epichlorohydrin

Each 0.4 mol % of the catalyst I-SS-1 prepared in Example 2, comparativecatalyst 2 having acetate group, and comparative catalyst 3 having bromogroup was added to 100 g of racemic epichlorohydrin separately andcooled to 5° C. 10.7 g of water was slowly added to each reactionmixture of which was stirred at 20° C. The optical purity of eachreaction mixture was measured over reaction time as shown in FIG. 3.

EXPERIMENTAL EXAMPLE 3

Preparation of (R)-epibromohydrin or (S)-epibromohydrin

2 g of the catalyst prepared in Example 1 (I-SS-1) or Example 2 (I-RR-1)was added to 148 g of racemic epibromohydrin and cooled to 5° C. 13.6 gof water was slowly added to the reaction mixture of which was stirredat 20° C. for 4 hrs. The reaction mixture was performed for fractionaldistillation under vacuum to obtain (R) (or (S))-epibromohydrin.Dichloromethane and water were added to the residue and extracted outthe used catalyst to the dichloromethane layer which was evaporatedunder vacuum to recover the used catalyst. The recovered catalyst wasused for next reaction without any activation process to produce (R) (or(S))-epibromohydrin with over 99% ee of optical purity.

EXPERIMENTAL EXAMPLE 4

Preparation of (S)-1,2-epoxybutane or (R)-1,2-epoxybutane

The reaction was performed in the same manner as Experimental Example 3except that 78 g of racemic 1,2-epoxybutane was used instead of racemicepibromohydrin to obtain the target product with over 99% ee of opticalpurity.

EXPERIMENTAL EXAMPLE 5

Preparation of (S)-1,2-epoxyhexane or (R)-1,2-epoxyhexane

The reaction was performed in the same manner as Experimental Example 3except that 108 g of racemic 1,2-epoxyhexane was used instead of racemicepibromohydrin to obtain the target product with over 99% ee of opticalpurity.

EXPERIMENTAL EXAMPLE 6

Preparation of (S)-styrene oxide or (R)-styrene oxide

5 g of the catalyst prepared in Example 1 (I-SS-1) or Example 2 (I-RR-1)was added to 130 g of racemic styrene oxide and cooled to 5° C. 13.6 gof water was slowly added to the reaction mixture, which was stirred at20° C. for 15 hrs. The reaction mixture was performed for fractionaldistillation under vacuum to obtain first (R) (or (S))-styrene oxide.Dichloromethane and water were added to the residue and extracted outthe used catalyst to the dichloromethane layer which was evaporatedunder vacuum to recover the used catalyst. The recovered catalyst wasreused for next reaction without any activation process to produce (R)(or (S))-styrene oxide with over 99% ee of optical purity.

EXPERIMENTAL EXAMPLE 7

Preparation of (S)-1,2-butandiol or (R)-1,2-butandiol

2 g of the catalyst prepared in Example 1 (I-SS-1) or Example 2 (I-RR-1)was added to 78 g of racemic 1,2-epoxybutane and cooled to 5° C. 7.8 gof water was slowly added to the reaction mixture, which was stirred at20° C. for 3 hrs. The reaction mixture was performed for fractionaldistillation under vacuum to obtain first (R) (or (S))-1,2-butandiol.Dichloromethane and water were added to the residue and extracted outthe used catalyst to the dichloromethane layer which was evaporatedunder vacuum to recover the used catalyst. The recovered catalyst wasreused for next reaction without any activation process to produce (R)(or (S))-1,2-butandiol with over 99% ee of optical purity.

As described above, the chiral salen catalyst of the present inventioncan be reused without any activation process, which is a disadvantageassociated with conventional chiral salen catalyst, and used in massproduction of chiral epoxides or chiral 1,2-dials from racemic epoxidesin high yield and high optical purity by stereoselective hydrolysis.

What is claimed is:
 1. A method of preparing chiral epoxides or chiral1,2-diols which comprises: stereoselectively hydrolyzing racemicepoxides using a chiral catalyst of formula (1),

wherein X₁, X₂, X₃, X₄, X₅, X₆, X₇, and X₈ represent independentlyhydrogen or C₄-C₁₀ alkyl; Y₁ and Y₂ represent independently hydrogen orC₁-C₅ alkyl; Z represents PF₆, or BF₄; and R₁ and R₂ independentlyrepresent hydrogen, C₄-C₁₀ alkyl, unsubstituted phenyl or C₁-C₄ alkylsubstituted phenyl, where one of R₁ and R₂ should be a hydrogen atom, orR₁ and R₂ are bonded to be —(CH₂)_(n)— (where n is an integer of 3 to 6)or —(CH₂)_(m)—Q—(CH₂)_(m)— (where m is an integer of 1 to 2 and Q is anoxygen atom or NH).
 2. The method of claim 1, wherein said X₁, X₂, X₃,X₄, X₅, X₆, X₇, and X₈ independently represent a hydrogen atom ort-butyl group; said Y₁ and Y₂ represent a hydrogen atom; said Zrepresents PF₆, or BF₄; and one of said R₁ and R₂ is a hydrogen atom andthe other is —(CH₂)₄—.